Synthesis and antiviral activity of HCV NS3/4A peptidomimetic boronic acid inhibitors

The synthesis and evaluation of a series of peptidomimetic boronic acid inhibitors of the HCV NS3/4A protease is described. Data on their biochemical and cellular activities, mutant protease activity, and genotype coverage is reported. A new series of NS3/4A protease boronic acid inhibitors is described. The compounds show good biochemical potency and cellular activity. The peptidomimetic inhibitors were evaluated against proteases from different HCV genotypes and clinically relevant NS3/4A mutants. Compound 28 displayed subnanomolar to single digit nanomolar potencies in the enzymatic assays and an EC 50 of 25 nM in the replicon cell-based assay.